Parenteral medium-chain triglyceride-induced neutrophil activation is not mediated by a Pertussis Toxin sensitive receptor.
OBJECTIVE
Lipid-induced immune modulation might contribute to the increased infection rate that is observed in patients using parenteral nutrition. We previously showed that emulsions containing medium-chain triglycerides (LCT/MCTs or pure MCTs), but not pure long-chain triglycerides (LCTs), impair neutrophil functions, modulate cell-signaling and induce neutrophil activation in vitro. It has recently been shown that medium-chain fatty acids are ligands for GPR84, a pertussis toxin (PT)-sensitive G-protein-coupled receptor (GPCR). This finding urged us to investigate whether MCT-induced neutrophil activation is mediated by PT-sensitive GPCRs.


METHODS
Neutrophils isolated from blood of healthy volunteers were pre-incubated with PT (0.5-1 microg/mL, 1.5 h) and analyzed for the effect of this pre-incubation on LCT/MCT (2.5 mmol/L)-dependent modulation of serum-treated zymosan (STZ)-induced intracellular Ca(2+) mobilization and on LCT/MCT (5 mmol/L)-induced expression of cell surface adhesion (CD11b) and degranulation (CD66b) markers and oxygen radical (ROS) production.


RESULTS
PT did not inhibit the effects of LCT/MCT on the STZ-induced increase in cytosolic free Ca(2+) concentration. LCT/MCT increased ROS production to 146% of unstimulated cells. However, pre-incubation with PT did not inhibit the LCT/MCT-induced ROS production. Furthermore, the LCT/MCT-induced increase in CD11b and CD66b expression (196% and 235% of unstimulated cells, respectively) was not inhibited by pre-incubation with PT.


CONCLUSIONS
LCT/MCT-induced neutrophil activation does not involve the action of a PT-sensitive G-protein-coupled receptor.
Versleijen
Michelle W J
MW
Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
van Esterik
Joantine C J
JC
Roelofs
Hennie M J
HM
van Emst-de Vries
Sjenet E
SE
Willems
Peter H G M
PH
Wanten
Geert J A
GJ
D039481:CD11b Antigen / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D005217:Fat Emulsions, Intravenous / Q000737:chemistry; D006801:Humans; D018375:Neutrophil Activation / Q000187:drug effects* / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010288:Parenteral Nutrition / Q000009:adverse effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D014280:Triglycerides / Q000737:chemistry / Q000494:pharmacology*; D015054:Zymosan / Q000494:pharmacology
D039481:CD11b Antigen; D005217:Fat Emulsions, Intravenous; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014280:Triglycerides; C093426:pertussis toxin receptor; D015054:Zymosan; D002118:Calcium